Despite high HIV prevalence among transgender women (TGW) in India, there is limited exploration of pre-exposure prophylaxis (PrEP) acceptability. With PrEP licensure pending, we conducted six focus group discussions (FGDs) with diverse TGW (n = 36), and eight key informant interviews with community leaders and physicians, in Mumbai and Chennai. Data were explored using framework analysis guided by the Theoretical Framework of Acceptability. FGD participants' mean age was 26.1 years (SD = 4.8); two-thirds engaged in sex work. TGW reported low PrEP awareness, with moderate acceptability once PrEP was explained. Population-specific facilitators of PrEP acceptability included its perceived effectiveness in the context of challenges to condom use in serodiscordant relationships and forced sex encounters. PrEP was considered especially appropriate for TGW sex workers; however, barriers were anticipated in the context of hierarchical hijra (indigenous trans identity) kinship networks and gurus' (masters) potential negative reactions to PrEP use by their chelas (disciples). Positive attitudes toward high efficacy and potential covert use were tempered by TGW's concerns about high costs and adherence challenges living with parents or primary partners, and TGW sex workers' unpredictable schedules. Anticipated interactions with feminizing hormones, visible side effects, and PrEP-related stigma within TGW communities emerged as opportunity costs. PrEP implementation for TGW in India should promote comprehensive information on side effects and potential interactions with feminizing hormones, provide free or subsidized PrEP, and highlight the advantages of added protection in sex work and forced sexual encounters. Meaningful engagement with TGW kinship networks can encourage positive transgender community norms on PrEP use and mitigate multifaceted stigma.
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